Is APOE p.Pro30= (c.90C>G) pathogenic?

APOE p.Pro30= (c.90C>G) is classified Likely benign in APOE (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-01-21). Ultra-rare (popmax 0.0378%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with APOE p.Pro30= (c.90C>G)?

APOE p.Pro30= (c.90C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is APOE p.Pro30= (c.90C>G) in the general population?

APOE p.Pro30= (c.90C>G) is ultra-rare (popmax 0.0378%, nfe) (gnomAD).

APOE p.Pro30=

c.90C>G · rs370227413 · VCV1209987

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0378%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.1	GERP -1.7
Overall
CADD	0.056	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0378% European (non-Finnish) · 446/1,179,948 alleles

Filtering AF 0.0348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0337%

Overall 0.029% 468/1,613,602 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0378%	2,646
Remaining individualsnot grpmax-eligible	0.0192%	5,205
African / African-American	0.00801%	12,484
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,592
Finnishnot grpmax-eligible	0.00314%	31,895
Admixed American	0.00167%	59,982

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: APOE
Protein: p.Pro30=
Coding: c.90C>G
MANE Select: NM_000041
dbSNP: rs370227413
Type: single nucleotide variant
Location: chr19:44907806 (GRCh38)
Gene constraint: LOEUF 1.319 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.13 · 31 PDB

Full APOE gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APOE p.Arg43Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
APOE p.Arg246Pro Uncertain significance ★★ same condition
APOE p.Arg56His Uncertain significance ★★ ⚠ same condition
APOE p.Gln119Pro Uncertain significance ★★ same condition
APOE p.Gln181His Uncertain significance ★★ ⚠ same condition
APOE p.Ser112Tyr Uncertain significance ★★ ⚠ same condition
APOE p.Trp294Cys Uncertain significance ★★ ⚠ same condition
APOE p.Val213Gly Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/apoe-p-pro30 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown